p53 overexpression is associated with cytoreduction and response to chemotherapy in ovarian cancer

The aim of this study was to assess the association of p53 status with primary cytoreduction, response to chemotherapy and outcome in stage III–IV primary ovarian cancer patients. Immunohistochemical analysis of p53 was performed on formalin-fixed, paraffin-embedded specimens from 168 primary ovarian carcinomas by using the DO-7 monoclonal antibody. p53 nuclear positivity was found in 84 out of 162 (52%) malignant tumours. A higher percentage of p53 nuclear positivity was observed in patients with advanced stage of disease than in stage I–II (57% vs 23% respectively; P = 0.0022) and in poorly differentiated versus well/moderately differentiated tumours (59% vs 32% respectively; P = 0.0038). The multivariate analysis aimed to investigate the association of FIGO stage, grade and p53 status with primary cytoreduction in 136 stage III–IV patients showed that stage IV disease may influence the possibility to perform primary cytoreduction in ovarian cancer patients. p53-positivity also maintained a trend to be associated with poor chance of cytoreduction. In patients who underwent pathologic assessment of response, cases who did not respond to chemotherapy were much more frequently p53-positive than p53-negative (86% vs 14% respectively; P = 0.012). Moreover, patients with stage III disease and < 2-cm residual tumour were more likely to respond to treatment. In multivariate analysis, FIGO stage and p53 expression were independently correlated with pathologic response to chemotherapy. Time to progression and survival rates were shown not to be different in p53-positive versus p53-negative patients. © 1999 Cancer Research Campaig

pO polarography, contrast enhanced color duplex sonography (CDS), [18F] fluoromisonidazole and [18F] fluorodeoxyglucose positron emission tomography: validated methods for the evaluation of therapy-relevant tumor oxygenation or only bricks in the puzzle of tumor hypoxia?

<p>Abstract</p> <p>Background</p> <p>The present study was conducted to analyze the value of ([¹⁸F] fluoromisonidazole (FMISO) and [¹⁸F]-2-fluoro-2'-deoxyglucose (FDG) PET as well as color pixel density (CPD) and tumor perfusion (TP) assessed by color duplex sonography (CDS) for determination of therapeutic relevant hypoxia. As a standard for measuring tissue oxygenation in human tumors, the invasive, computerized polarographic needle electrode system (pO₂histography) was used for comparing the different non invasive measurements.</p> <p>Methods</p> <p>Until now a total of 38 Patients with malignancies of the head and neck were examined. Tumor tissue pO₂was measured using a pO₂-histograph. The needle electrode was placed CT-controlled in the tumor without general or local anesthesia. To assess the biological and clinical relevance of oxygenation measurement, the relative frequency of pO₂readings, with values ≤ 2.5, ≤ 5.0 and ≤ 10.0 mmHg, as well as mean and median pO₂were stated. FMISO PET consisted of one static scan of the relevant region, performed 120 min after intravenous administration. FMISO tumor to muscle ratios (FMISO_T/M) and tumor to blood ratios (FMISO_T/B) were calculated. FDG PET of the lymph node metastases was performed 71 ± 17 min after intravenous administration. To visualize as many vessels as possible by CDS, a contrast enhancer (Levovist^®, Schering Corp., Germany) was administered. Color pixel density (CPD) was defined as the ratio of colored to grey pixels in a region of interest. From CDS signals two parameters were extracted: color hue – defining velocity (v) and color area – defining perfused area (A). Signal intensity as a measure of tissue perfusion (TP) was quantified as follows: TP = v_mean× A_mean.</p> <p>Results</p> <p>In order to investigate the degree of linear association, we calculated the Pearson correlation coefficient. Slight (|r| > 0.4) to moderate (|r| > 0.6) correlation was found between the parameters of pO₂polarography (pO₂readings with values ≤ 2.5, ≤ 5.0 and ≤ 10.0 mmHg, as well as median pO₂), CPD and FMISO_T/M. Only a slight correlation between TP and the fraction of pO₂values ≤ 10.0 mmHg, median and mean pO₂could be detected. After exclusion of four outliers the absolute values of the Pearson correlation coefficients increased clearly. There was no relevant association between mean or maximum FDG uptake and the different polarographic- as well as the CDS parameters.</p> <p>Conclusion</p> <p>CDS and FMISO PET represent different approaches for estimation of therapy relevant tumor hypoxia. Each of these approaches is methodologically limited, making evaluation of clinical potential in prospective studies necessary.</p

Is radical innovation in architecture crucial to sustainability? Lessons from three Scottish contemporary buildings

Radical innovation is largely recognised as a medium for advancement, a source of growth for economies, and a trigger for progress in different economic sectors. Often, this type of innovation is identified with technological advancements, disruptive phenomena and the creation of new systems and dynamics. Yet, within the context of a changing world, in which principles of economic, environmental and social sustainability are largely adopted as common objectives, a reflection on the type of progress and the need for radical innovation is necessary with the aim of informing on their impacts and effectiveness. This work presents an analysis of a number of contemporary Scottish architectural designs, developed under the aegis of sustainability principles, and explores the types of sustainable innovations introduced and the results achieved by analyzing the type of design change that triggered specific sustainable results, demonstrating alternative innovation strategies, other than the radical one. This analysis provides a basis for discussion on the need for radical innovation in the context of sustainable architecture and explores the role of other types of innovation against the results achieved. This discussion could contribute to a better understanding of the current state of practice in architectural design, as well as in policy making in regard to the design and management of the future built environment

Ovarian damage from chemotherapy and current approaches to its protection

BACKGROUND: Anti-cancer therapy is often a cause of premature ovarian insufficiency and infertility since the ovarian follicle reserve is extremely sensitive to the effects of chemotherapy and radiotherapy. While oocyte, embryo and ovarian cortex cryopreservation can help some women with cancer-induced infertility achieve pregnancy, the development of effective methods to protect ovarian function during chemotherapy would be a significant advantage.OBJECTIVE AND RATIONALE: This paper critically discusses the different damaging effects of the most common chemotherapeutic compounds on the ovary, in particular, the ovarian follicles and the molecular pathways that lead to that damage. The mechanisms through which fertility-protective agents might prevent chemotherapy drug-induced follicle loss are then reviewed.SEARCH METHODS: Articles published in English were searched on PubMed up to March 2019 using the following terms: ovary, fertility preservation, chemotherapy, follicle death, adjuvant therapy, cyclophosphamide, cisplatin, doxorubicin. Inclusion and exclusion criteria were applied to the analysis of the protective agents.OUTCOMES: Recent studies reveal how chemotherapeutic drugs can affect the different cellular components of the ovary, causing rapid depletion of the ovarian follicular reserve. The three most commonly used drugs, cyclophosphamide, cisplatin and doxorubicin, cause premature ovarian insufficiency by inducing death and/or accelerated activation of primordial follicles and increased atresia of growing follicles. They also cause an increase in damage to blood vessels and the stromal compartment and increment inflammation. In the past 20 years, many compounds have been investigated as potential protective agents to counteract these adverse effects. The interactions of recently described fertility-protective agents with these damage pathways are discussed.WIDER IMPLICATIONS: Understanding the mechanisms underlying the action of chemotherapy compounds on the various components of the ovary is essential for the development of efficient and targeted pharmacological therapies that could protect and prolong female fertility. While there are increasing preclinical investigations of potential fertility preserving adjuvants, there remains a lack of approaches that are being developed and tested clinically

When more is not better: 10 'don'ts' in endometriosis management. An ETIC* position statement

41noETIC Endometriosis Treatment Italian ClubopenA network of endometriosis experts from 16 Italian academic departments and teaching hospitals distributed all over the country made a critical appraisal of the available evidence and definition of 10 suggestions regarding measures to be de-implemented. Strong suggestions were made only when high-quality evidence was available. The aim was to select 10 low-value medical interventions, characterized by an unfavorable balance between potential benefits, potential harms, and costs, which should be discouraged in women with endometriosis. The following suggestions were agreed by all experts: do not suggest laparoscopy to detect and treat superficial peritoneal endometriosis in infertile women without pelvic pain symptoms; do not recommend controlled ovarian stimulation and IUI in infertile women with endometriosis at any stage; do not remove small ovarian endometriomas (diameter &lt;4&nbsp;cm) with the sole objective of improving the likelihood of conception in infertile patients scheduled for IVF; do not remove uncomplicated deep endometriotic lesions in asymptomatic women, and also in symptomatic women not seeking conception when medical treatment is effective and well tolerated; do not systematically request second-level diagnostic investigations in women with known or suspected non-subocclusive colorectal endometriosis or with symptoms responding to medical treatment; do not recommend repeated follow-up serum CA-125 (or other currently available biomarkers) measurements in women successfully using medical treatments for uncomplicated endometriosis in the absence of suspicious ovarian cysts; do not leave women undergoing surgery for ovarian endometriomas and not seeking immediate conception without post-operative long-term treatment with estrogen-progestins or progestins; do not perform laparoscopy in adolescent women (&lt;20&nbsp;years) with moderate-severe dysmenorrhea and clinically suspected early endometriosis without prior attempting to relieve symptoms with estrogen-progestins or progestins; do not prescribe drugs that cannot be used for prolonged periods of time because of safety or cost issues as first-line medical treatment, unless estrogen-progestins or progestins have been proven ineffective, not tolerated, or contraindicated; do not use robotic-assisted laparoscopic surgery for endometriosis outside research settings. Our proposal is to better address medical and surgical approaches to endometriosis de-implementing low-value interventions, with the aim to prevent unnecessary morbidity, limit psychological distress, and reduce the burden of treatment avoiding medical overuse and allowing a more equitable distribution of healthcare resources.openAlio, L; Angioni, S; Arena, S; Bartiromo, L; Bergamini, V; Berlanda, N; Bonin, C; Busacca, M; Candiani, M; Centini, G; D’Alterio, M N; Di Cello, A; Exacoustos, C; Fedele, L; Frattaruolo, M P; Incandela, D; Lazzeri, L; Luisi, S; Maiorana, A; Maneschi, F; Martire, F; Massarotti, C; Mattei, A; Muzii, L; Ottolina, J; Perandini, A; Perelli, F; Pino, I; Porpora, M G; Raimondo, D; Remorgida, V; Seracchioli, R; Solima, E; Somigliana, E; Sorrenti, G; Venturella, R; Vercellini, P; Viganó, P; Vignali, M; Zullo, F; Zupi, EAlio, L; Angioni, S; Arena, S; Bartiromo, L; Bergamini, V; Berlanda, N; Bonin, C; Busacca, M; Candiani, M; Centini, G; D’Alterio, M N; Di Cello, A; Exacoustos, C; Fedele, L; Frattaruolo, M P; Incandela, D; Lazzeri, L; Luisi, S; Maiorana, Anna; Maneschi, F; Martire, F; Massarotti, C; Mattei, A; Muzii, L; Ottolina, J; Perandini, A; Perelli, F; Pino, Ida; Porpora, M G; Raimondo, D; Remorgida, V; Seracchioli, R; Solima, E; Somigliana, E; Sorrenti, G; Venturella, R; Vercellini, P; Vigano', Paola; Vignali, M; Zullo, F; Zupi,

Dyslexia as a potential aspect of neurocognitive impairment in Schizophrenia: a pilot neuropsychological study"

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